基于P-gp功能的多药耐药逆转剂高内涵筛选方法的建立与应用  

Establishment and application of high content screening for assaying P-gp

作　　者：郑婷婷[1] 李敏[1] 徐波[1] 崔景荣[1] 

机构地区：[1]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191

出　　处：《中国新药杂志》2010年第10期861-866,共6页Chinese Journal of New Drugs

摘　　要：目的:建立灵敏、快速、稳定的检测P-糖蛋白(P-gp)功能的高内涵筛选模型,寻找高效、低毒的肿瘤多药耐药逆转剂。方法:以荧光探针JC-1在耐药细胞内蓄积实验为基础,建立基于细胞的高内涵筛选模型。结果:JC-1的最佳使用浓度为0.5μmol.L-1,为RHO123浓度的1/10;同时,JC-1染色稳定性好、所建模型Z因子达0.8,明显优于RHO123组。利用该模型筛选获得了多个能抑制P-gp功能的化合物。结论:所建立的P-gp蛋白功能抑制剂高内涵筛选模型具有灵敏、简便与稳定等特点,可用于药物筛选。Objective：To establish a high content screening（HCS） method assaying P-glycoprotein（P-gp） activity,by which to screen the effective and low-toxic agents against multidrug resistance（MDR）.Methods： The HCS-assay was based on the accumulating experiment in JC-1 in drug-resistant cells,and used to detect compounds in the cellular level.Results： The optimal concentration of JC-1 used in the screening assay was 0.5μmol·L-1 that was only 1/10 of RHO123.Besides,JC-1 was more stable than RHO123.The Z factor of the assay was 0.8 that was higher than RHO123.The compounds inhibiting P-gp were obtained by the assay.Conclusion： The HCS method assaying P-gp activity is sensitive,specific and stable,which could be used for the screening of MDR-reversing agents.

关 键 词：P-糖蛋白 JC-1 多药耐药 高内涵筛选 

分 类 号：R965.1[医药卫生—药理学]